KR102122185B1 - Sunscreen compositions containing an ultraviolet radiation-absorbing polymer - Google Patents

Abstract

Discontinuous oil phase homogeneously dispersed in continuous aqueous phase, oil phase containing sunscreen agent comprising polymer composition containing linear ultraviolet radiation absorbing polyether, linear ultraviolet radiation absorbing polyether comprising chemically bound UV-chromophore ; And an oil-in-water emulsifier component comprising an anionic oil-in-water emulsifier in an amount such that the composition comprises from about 0.5% to about 3% by weight of the anionic oil-in-water emulsifier.

Description

Sunscreen composition containing UV radiation-absorbing polymers {SUNSCREEN COMPOSITIONS CONTAINING AN ULTRAVIOLET RADIATION-ABSORBING POLYMER}

This application claims the benefit of U.S. Provisional Application No. 61/665,464 filed June 28, 2012, the entire disclosure of which is incorporated herein by reference for all purposes.

The present invention relates to topically acceptable sunscreen compositions comprising UV-absorbing polyethers.

Prolonged exposure to ultraviolet (UV) radiation, such as from the sun, can lead to photo dermatitis and the formation of erythema, in addition to increasing the risk of skin cancer, such as melanoma, and aging of the skin, eg, skin It can accelerate loss of elasticity and wrinkles.

A number of sunscreen compositions are commercially available with various abilities to shield the body from ultraviolet light. However, a number of problems still exist in providing a sunscreen composition that provides strong UV radiation protection.

For example, the problem in creating a sunscreen having various properties such as mildness is further amplified when additional restrictions are imposed on the sunscreen composition. The present invention provides a mild and aesthetic sunscreen composition comprising a polymeric sunscreen compound.

According to one aspect, the composition of the present invention comprises a discontinuous oil phase comprising a sunscreen agent comprising a polymer composition comprising a linear ultraviolet radiation absorbing polyether comprising a chemically bound UV-chromophore. The discontinuous oil phase is homogeneously distributed in the continuous water phase. The composition further comprises an oil-in-water emulsifier component comprising an anionic oil-in-water emulsifier in an amount from about 0.5% to about 3% by weight of the composition.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. As used herein, unless otherwise indicated, all hydrocarbon groups (eg, alkyl, alkenyl groups) can be straight or branched chain groups. As used herein, unless indicated otherwise, the term “molecular weight” refers to weight average molecular weight (Mw).

Unless otherwise defined, all concentrations refer to concentrations by weight of the composition. In addition, unless specifically defined otherwise, the term “essentially inclusive” with respect to the class of ingredients is that the particular ingredient(s) is in a concentration less than is necessary for the particular ingredient to be effective in providing benefits or properties. This is present, and for this it would otherwise be used, for example, about 1% or less or about 0.5% or less.

As used herein, “UV-absorbing” refers to a material or compound that absorbs radiation in a portion of the ultraviolet spectrum (290 nm to 400 nm), for example, a polymeric or non-polymeric sunscreen agent or a chemical moiety (E.g., having an absorption coefficient of at least about 1000 mol ^-1 cm ^-1 for one or more wavelengths within the ultraviolet spectrum defined above). SPF values disclosed and claimed herein are determined using the in vitro method described herein below.

UV-absorbing polyether

Embodiments of the invention relate to compositions comprising ultraviolet radiation absorbing polyethers (ie, “UV absorbing polyethers”). UV absorbing polyether means a polyether that absorbs radiation in some part of the ultraviolet spectrum (wavelength between 290 and 400 nm). UV absorbing polyethers have a weight average molecular weight (M _w ) that may be suitable to reduce or prevent chromophores from being absorbed through the skin. According to one embodiment, a suitable molecular weight of the UV absorbing polyether is M _w >500. In one embodiment, M _w is in the range of about 500 to about 50,000. In other embodiments, M _w is in the range of about 1,000 to about 20,000, for example, about 1,000 to about 10,000.

Compositions comprising UV-absorbing polyethers are described herein. As will be appreciated by those skilled in the art, “polyether” indicates that the UV absorbing polymer comprises a plurality of ether functional groups covalently bonded to each other. The “skeleton” of UV-absorbing polyether refers to the longest continuous sequence of covalently linked ether functional groups. Another smaller group of covalent bonding atoms is considered a pendant group branching from the backbone.

According to certain embodiments, UV-absorbing polyethers include glyceryl repeat units, and thus can be characterized as polyglycerols. “Glyceryl repeating unit” (also referred to herein as “glyceryl remnant unit”) means a glycerol unit excluding nucleophilic groups such as hydroxyl groups. Glyceryl residue units contain ether functional groups and can generally be represented as C ₃ H ₅ O for linear and dendritic residues (Rokicki et al. Green Chemistry ., 2005, 7, 52). ). Suitable glyceryl residue units are the following glyceryl units: linear-1,4 (L _1,4 ) glyceryl units; Linear-1,3 (L _1,3 ) glyceryl repeat units; Dendritic (D) glyceryl units; Terminal-1,2 (T _1,2 ) units; And terminal-1,3 (T _1,3 ) units in dehydrated form (ie, 1 mole of water is removed). Examples of linear glyceryl residue units and terminal units are shown below (to the right of the arrows). Corresponding glyceryl units before dehydration (shown on the left side of the arrow; including hydroxyl) are also shown:

Linear-1,4 (L _1,4 ) glyceryl repeat unit

Linear-1,3 (L _1,3 ) glyceryl repeat unit

Terminal-1,2 (T _1,2 ) units

And terminal-1,3 (T _1,3 ) units

The composition comprises a linear UV-absorbing polyether comprising a chemically bound ultraviolet radiation-absorbing chromophore (“UV-chromophore”). Linear means that the UV-absorbing polyether has an unbranched skeleton.

According to certain embodiments, the linear UV-absorbing polyether comprises any or both of the repeating units shown in Formulas IA and IIB:

Formula IA. Repeat unit of linear UV-absorbing polyether

Formula IIB. Repeat unit of linear UV-absorbing polyether

In Formulas IA and IIB, Y represents a UV-chromophore as described below. Illustrative examples of linear UV-absorbing polyethers comprising chemically bound UV-chromophores are shown in Formula IIIC.

Formula IIIC. Linear UV absorption polyether

In the structure illustrated in Formula IIIC, X is either a terminal functional group or part of a polymer backbone; R is a pendant group attached to the polymer backbone, and X is an end group.

X and R may be the same or different. X and R can be independently selected from, for example, hydrogen, linear alkyl, alkenyl or alkynyl hydrocarbon chains, linear siloxanes, and the like. In one embodiment, group X represents octadecane. Y represents a UV-chromophore and groups represented by Y are described below. The proportion of ether repeat units having substituent Y is a real number represented by the following equation (1):

Equation 1

In the above formula, both m and n represent real numbers between 0 and 1, and the sum of n and m is 1. In one embodiment, the value m is 1 and n is 0 (UV-absorbing polyether is a homopolymer and includes repeating units of formula IA). In other embodiments, the value m <1 (the polymer is a copolymer having R and Y pendant groups). For copolymers containing both R and Y pendant groups, the distribution of pendant R and Y groups along the polymer chain can be altered to obtain optimal polymer properties. In one embodiment, the UV-absorbing polyether is a random copolymer, and the groups R and Y are statistically distributed along the polymer chain. In another embodiment, the UV-absorbing polyether is a block copolymer composed of alternating segments of polymer backbone functionalized with a larger proportion of R or Y. In other embodiments, the distribution of pendant groups R and Y along the polymer backbone is somewhere between the boundary conditions of the block copolymer and the statistical random copolymer. In formula IIIC, the integers o and p represent the number of CH ₂ groups in the repeating unit having Y and R.

Introduction of various R pendant groups can be achieved by using different comonomers during the polymerization reaction. The physical properties and chemical properties of the final UV-absorbing polyether can be changed by varying the size, chemical composition, weight percent, and position of the backbone of these comonomers. Examples of comonomers that may be included in UV-absorbing polyethers include, but are not limited to, ethylene oxide, propylene oxide, and glycidyl ethers, such as n-butyl glycidyl ether, 2-ethylhexylglycidyl ether. It is not limited.

It is apparent to those skilled in the art that polyethers of the type illustrated in Formulas IA, IIB, and IIIC can be obtained through various synthetic routes. Among such routes is ring-opening polymerization of cyclic ether monomers and optional comonomers. The ring size of the cyclic ether monomer determines the value of o or p , and the resulting framework structure of the UV-absorbing polyether. For monomers or comonomers that are epoxides (a ternary ring containing 2 carbon atoms and 1 oxygen atom), the value of o or p in the resulting UV-absorbing polyether is 1. The repeating units produced using epoxide comonomers are shown in Structure A of Formula IV. For (co)monomers, which are oxetane (a four-membered ring containing three carbon atoms and one oxygen atom), the value of o or p in the resulting UV absorbing polyether is 2. The repeating units produced using oxetane comonomers are shown in Structure B of Formula IV. The length of the alkyl chain in each monomer type can be selected to alter the properties of the UV-absorbing polyether. In one embodiment, both o and p are 1. An example of such a case is where the repeating units with Y and R are both from epoxide monomers ( o = p = 1), or both from oxetane monomers ( o = p = 2). In other embodiments, o and p are not the same. An example of this case is the case where the repeating unit with UV-chromophore Y is based on the epoxide monomer ( o = 1), and the repeating unit with group R is based on the oxetane monomer ( p = 2).

Formula IV. Random repeat unit

Suitable UV-chromophores that can be chemically bound in the UV-absorbing polyethers of the present invention include UV-absorbing triazoles (moiety containing 5-membered heterocyclic rings with 2 carbon atoms and 3 nitrogen atoms). ), for example, benzotriazole. In other embodiments, the structure represented by Y contains or has a pendant UV-absorbing triazine (a 6-membered heterocycle containing 3 nitrogen atoms and 3 carbon atoms). Suitable UV-chromophores include those having absorbance of UVA radiation. Other suitable UV-chromophores are those that absorb in the UVB region. In one embodiment, the UV-chromophore absorbs in both UVA and UVB regions. In one embodiment, if the UV absorbing polyether is cast into a film, as measured with respect to at least one wavelength within the wavelength range of about 1,000 mol ^-1 cm ^-1 or more, preferably from about 2,000 mol ^-1 cm ^- It is possible to produce a molar extinction coefficient of at least ¹ , more preferably at least about 4,000 mol ^-1 cm ^-1 . In one embodiment, the molar extinction coefficient at 40% or more of the wavelength in this portion of the spectrum is at least about 1000 mol ^-1 cm ^-1 . Examples of UV-chromophores that absorb UVA include triazoles such as benzotriazoles such as hydroxyphenyl-benzotriazole; Camphor, eg benzylidene camphor and derivatives thereof (eg terephthalidene dicamphor sulfonic acid); Dibenzoylmethane and derivatives thereof.

In one embodiment, the UV-chromophore is a benzotriazole that provides both light stability and strong UVA absorption, having the structure represented by Formula V.

Formula V. Benzotriazole UV-absorbing chromophore

Wherein each R ₁₄ is independently selected from the group consisting of hydrogen, C ₁ to C ₂₀ alkyl, alkoxy, acyl, alkyloxy, alkylamino, and halogen; R ₁₅ is independently selected from the group consisting of hydrogen, C ₁ to C ₂₀ alkyl, alkoxy, acyl, alkyloxy, and alkylamino, and R ₂₁ is C ₁ to C ₂₀ alkyl, alkoxy, acyl, alkyloxy, and alkyl Amino. Either the R ₁₅ group or the R ₂₁ group can include a functional group that can be attached to the polymer. Compounds similar to the structure of Formula V are described in U.S. Pat.No. 5,869,030, methylene bis-benzotriazolyl tetramethylbutylphenol (trade name tinsorb by BASF Corporation, Wyandotte, Michigan) (TINSORB) compound sold as M). In one embodiment, the UV-absorbing triazole is 3-(3-(2H-benzo[d][1,2,3]tri, commercially available as TINUVIN 213, also available from BASF. Azole-2-yl)-5-(tert-butyl)-4-hydroxyphenyl) from the transesterification product of propanoic acid and polyethylene glycol 300. In another embodiment, the UV-absorbing triazole is benzenepropanoic acid, 3-(2H-benzotriazole-2-yl)-5-(1, 1-di, commercially available as Tinuvin 99, also available from BASF. methylethyl) -4-hydroxy -, C ₇ - ₉ - minutes a branched and linear alkyl esters. In other embodiments, the UV-absorbing group contains a triazine moiety. An exemplary triazine is 6-octyl-2-(4-(4,6-di([1,1'-biphenyl]-4-yl)-1,3,5-triazine-2-yl)- 3-hydroxyphenoxy) propanoate (a compound sold under the trade name Tinuvin 479 by BASF Corporation, Wyandotte, Michigan), trioctyl 2,2',2"-(((1,3, 5-triazine-2,4,6-triyl) tris(3-hydroxybenzene-4,1-diyl))tris(oxy)) tripropanoate.

In other embodiments, the UV-chromophore is a UVB-absorbing moiety. The UVB-absorbing chromophore means that the UV-chromophore has absorbency in the UVB portion (290 to 320 nm) of the ultraviolet spectrum. In one embodiment, the criteria for what is considered as a UVB-absorbing chromophore are similar to those described above for a UVA-absorbing chromophore, except that the wavelength range is 290 nm to 320 nm. Examples of suitable UVB-absorbing chromophores include 4-aminobenzoic acid and its alkane esters; Anthranilic acid and alkanes esters thereof; Salicylic acid and its alkane esters; Hydroxycinnamic acid and alkane esters thereof; Dihydroxy-, dicarboxy-, and hydroxycarboxybenzophenones and alkane esters or acid halide derivatives thereof; Dihydroxy-, dicarboxy-, and hydroxycarboxycalcones and alkane esters or acid halide derivatives thereof; Dihydroxy-, dicarboxy-, and hydroxycarboxycoumarin and alkanes esters or acid halide derivatives thereof; Benzalmalonate (benzylidene malonate); Benzimidazole derivatives (eg, phenyl benzimidazole sulfonic acid, PBSA), benzoxazole derivatives, and other suitably functionalized species capable of copolymerization within the polymer chain. In other embodiments, the UV absorbing polyether comprises more than one UV-chromophore or more than one chemical class of UV-chromophores.

UV-absorbing polyethers useful in the present invention can be synthesized by ring-opening polymerization of a suitable cyclic ether monomer to form a polyether, according to certain embodiments, followed by covalent attachment of the UV-chromophore to the pendant functional group ("after polymerization" Post-polymerization attachment. According to certain other embodiments, UV absorbing polyethers can be synthesized by polymerization of a cyclic ether monomer in which the monomer itself comprises a covalently attached UV-chromophore (ie, "directly". polymerization").

Additionally, as will be appreciated by those skilled in the art, UV-absorbing polyethers useful in the topical compositions of the present invention are prepared through polymer synthesis. The synthesis of UV absorbing-polyethers in general produces reaction products that are mixtures of UV-absorbing polyethers of various molecular weights, hereinafter referred to herein as "polymer compositions". The polymer composition may further include a small amount of unpolymerized material (in addition to the UV-absorbing polyether), which can be removed using techniques known in the art. According to certain embodiments, unpolymerized materials (e.g., partially reacted or unreacted monomers or other reactants) are included in the topical compositions of the present invention, e.g., using solvent extraction or supercritical CO ₂ purification. It can be partially or completely removed prior to becoming.

According to certain embodiments, the polymer composition to be included in the topical composition of the present invention comprises at least about 50% linear UV-absorbing polyethers comprising chemically bound UV-chromophores. According to certain other embodiments, the polymer composition comprises at least about 75% of a linear UV-absorbing polyether comprising a chemically bound UV-chromophore. According to certain other embodiments, the polymer composition comprises at least about 90% linear UV-absorbing polyether, for example at least about 95%. According to certain other embodiments, in addition to the linear UV-absorbing polyether, the polymer composition comprises a non-hyperbranched branched UV-absorbing polyether. In other embodiments, the polymer composition is substantially free of hyperbranched UV-absorbing polyethers, e.g., less than about 1% by weight, e.g., less than about 0.1% by weight of hyperbranched UV-absorbing polyethers. And completely free of, for example, hyperbranched UV-absorbing polyethers.

According to certain embodiments, the present polymer composition has low polydispersity. For example, the polydispersity index of the present polymer composition may be about 1.5 or less, for example about 1.2 or less. The polydispersity index is defined as M _w /M _N (ie, number average molecular weight, weight average molecular weight to M _N , ratio of M _w ). According to certain other embodiments, the polymer composition comprises at least 50% by weight of certain UV-absorbing polyether molecules.

The polydispersity of the present polymer composition can be kept low using certain synthetic procedures, for example, ring-opening polymerization and deprotection of cyclic ether monomers (described below). Alternatively, or additionally, the polymer composition may be treated using techniques known in the art to purify the polymer composition, such as supercritical CO ₂ (eg, prior to attachment of the UV-chromophore). Or later).

Synthesis of linear UV-absorbing polyethers by post-polymerization attachment of UV-chromophores comprises: ring-opening polymerization of cyclic ether monomers to form polyethers having protected groups; Deprotecting the polyether to remove at least a portion of the protected groups; And attaching the UV-chromophore to the deprotected UV-absorbing polyether, thereby forming a UV-absorbing polyether having a chemically bound UV chromophore.

An example of linear UV-absorbing polyether formation by post-polymerization adhesion is schematically illustrated in Formula VI. Initiation (I) is used to induce polymerization of the cyclic ether monomer (M), resulting in a polymer (P ₀ ) wherein the pendant hydroxy functionality is protected with a protecting group (P). The polymer (P ₀ ) is subjected to a condition for removing the protecting group (P), thereby obtaining a deprotected polymer (P _d ). Finally, by attaching a UV- chromophore (Y) pendant hydroxyl groups of the polymer (P _d), to obtain the final polymer (P _f) desired.

Formula VI. Synthesis of UV-absorbing chromophores by functionalization after polymerization

Ring-opening polymerization of cyclic ethers such as monomer (M) in formula (VI) can be accomplished using a variety of methods including cationic and anionic ring-opening polymerizations. In one embodiment, polymerization is carried out by anionic ring-opening polymerization. The monomer (M) in formula VI is in the form of glycidol, where the primary hydroxy group is masked with a protecting group (P). Polymerization of unprotected glycidol results in the formation of highly branched polymers (US Pat. No. 7988953B2, Tokar, R. et. al. Macromolecules 1994, 27 , 320-322); Sunder, A et al. Macromolecules 1999: 4240-4246; Rokicki, G. et.al. Green Chemistry 2005, 7 , 529). Conversely, anionic polymerization of glycidol derivatives with primary hydroxyl group protection can produce linear polyethers as exemplified by structure (P ₀ ) in Formula VI (Taton, D. et. al. Macromolecular Chemistry and Physics 1994, 195 , 139-148; Erberich, M. et.al. Macromolecules 2007, 40 , 3070-3079; Haouet, A. et.al. European Polymer Journal 1983, 19 , 1089-1098; Obermeier, B. et.al Bioconjugate Chemistry 2011, 22 , 436-444; Lee, BF et.al. Journal of polymer science.Part A, Polymer chemistry 2011, 49 , 4498-4504]). Protected cyclic ether monomers are not limited to epoxide derivatives and include functionalized cyclic ethers containing 3 to 6 consecutively adjacent atoms; In another embodiment, the monomer (M) is an oxetane derivative containing a protected primary hydroxyl group.

'Protected' means that the functional group in the multifunctional molecule is selectively derivatized by a portion that prevents covalent alteration in that functional group. The portion used as the protecting group is typically attached to the desired functional group in excellent chemical yield, and the good yield can be selectively removed as required, revealing the original functional group. Hydroxyl protecting groups include ethers such as methyl, methoxylmethyl (MOM), methylthiomethyl (MTM), t-butylthiomethyl, (phenyldimethylsilyl)methoxymethyl (SMOM), benzyloxymethyl (BOM) ), p-methoxybenzyloxymethyl (PMBM), (4-methoxyphenoxy)methyl (p-AOM), t-butoxymethyl, 4-pentenyloxymethyl (POM), siloxymethyl, 2- Methoxyethoxymethyl (MEM), 2,2,2-trichloroethoxymethyl, bis(2-chloroethoxy)methyl, 2-(trimethylsilyl)ethoxymethyl (SEMOR), tetrahydropyranyl ( THP), allyl, 3-bromotetrahydropyranyl, tetrahydrothiopyranyl, 1-methoxycyclohexyl, benzyloxy-2-fluoroethyl, 2,2,2-trichloroethyl, 2-trimethyl Silylethyl, 2-(phenylselenyl)ethyl, t-butyl, allyl, p-chlorophenyl, p-methoxyphenyl, 2,4-dinitrophenyl, benzyl, p-methoxybenzyl, 3,4-di Methoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6-dichlorobenzyl, trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), t -Butyldimethylsilyl (TBDMS), t-butyldiphenylsilyl (TBDPS), tribenzylsilyl, esters such as formate, benzoylformate, acetate, chloroacetate, dichloroacetate, trichloroacetate, tri Fluoroacetate, methoxyacetate, triphenylmethoxyacetate, phenoxyacetate, p-chlorophenoxyacetate, 3-phenylpropionate, 4-oxopentanoate (levulinate), 4,4-(ethylene Dithio)pentanoate (levulinoyldithioacetal), pivaloate, adamantate, crotonate, 4-methoxycrotonate, benzoate, p-phenylbenzoate, 2,4,6 -Trimethylbenzoate (mesitoate), and carbonates such as alkyl methyl carbonate, 9-fluorenylmethyl carbonate (Fmoc), alkyl ethyl carbonate, alkyl 2,2, 2-trichloroethyl carbonate (Troc), 2-(trimethylsilyl)ethyl carbonate (T MSEC), 2-(phenylsulfonyl)ethyl carbonate (Psec), 2-(triphenylphosphonio) ethyl carbonate (Peoc), alkyl isobutyl carbonate. In one embodiment, the protecting group is ethoxyethyl ether; In other embodiments, the protecting group is allyl ether.

Removal of the protecting group from the protected linear polyether (P ₀ ) to produce the deprotected polymer P( _d ) is accomplished using a method complementary to the selection of the protecting group (P); Such methods are familiar to those skilled in the art. In one embodiment, the primary hydroxyl group of the cyclic ether monomer is protected as 1-ethoxyethyl ether; Separation of these protecting groups to produce a deprotected polymer is achieved using aqueous acidic conditions such as aqueous acetic acid, aqueous hydrochloric acid, or acidic ion exchange resins. In other embodiments, the primary hydroxyl group of the cyclic ether monomer is protected as an allyl ether; Separation of these protecting groups to produce a deprotected polymer involves isomerization of allyl ether with vinyl ether followed by treatment with potassium alkoxide, followed by treatment with an acidic aqueous solution, isomerization with a transition metal catalyst, followed by acidic hydrolysis, Or by direct removal using a palladium (0) catalyst and a nucleophilic scavenger.

Anionic ring-opening polymerization of the monomer (M) illustrated in formula (VI) is initiated by an alkoxide salt (I). Examples of alkoxides suitable for initiating ring-opening polymerization of cyclic ether monomers include, but are not limited to, carbinol terminated polysiloxanes, polyethylene glycol methyl ethers, and potassium salts of linear C ₃ to C ₃₀ hydrocarbon alcohols. In one embodiment, the initiator for anionic ring-opening polymerization is the potassium salt of octadecanol. Other embodiments of the invention include polyoxyalkylenes such as polyethylene glycol, polypropylene glycol or poly(tetramethylene ether) glycol; Polyesters such as poly(ethylene adipate), poly(ethylene succinate); Copolymers having both oxyalkylene and ester functionalities on the backbone, for example poly[di(ethylene glycol) adipate]; And low molecular weight alcohols such as 1,4-butanediol, 1,6-hexanediol, or neopentyl glycol.

Depending on the functional group pendant from the polyether, chromophores can be covalently attached to the polymer backbone using a variety of methods known to those skilled in the art. The following method is exemplary and does not represent an exclusive list of possible means of attaching the UV-chromophore to the polymer backbone. For polymers with free hydroxyl groups (as represented by structure (P _d ) in Formula VI), UV-chromophores containing carboxylate groups can be covalently attached to the polymer using a number of methods familiar to those skilled in the art. have. Using a condensation reagent, a covalent bond can be formed between the UV-chromophore having a carboxylic acid and a hydroxyl group on the polymer to create an ester bond; In one embodiment, the condensation reagent is N - (3- dimethylaminopropyl) - N '- this is a mid-dihydro-chloride than ethyl carbonate. The carboxylic acid of the UV-chromophore can also be attached to the hydroxyl group on the polymer via ester linkage using transition metal catalysis; In one embodiment, the catalyst is tin(II) ethylhexanoate. The UV-chromophore can also be attached to the polymer by converting the carboxylic acid of the UV-chromophore to the corresponding acid chloride; Acid chloride reacts with hydroxyl groups on the functional polymer to form ester bonds; In one embodiment, this conversion to acid chloride is performed using thionyl chloride. UV-chromophore carboxylic acids can also be converted to isocyanates through the Curtis rearrangement of the intermediate acid azide; The chromophore isocyanate reacts with hydroxyl groups on the functional polymer to form urethane bonds. In other embodiments, the carboxylic acids on the UV-chromophore are converted to esters and can be attached to hydroxyl groups on the backbone by transesterification. This can be achieved by converting the carboxylic acid to an ester using a low boiling point alcohol such as methanol; The transesterification is carried out by reacting the chromophore ester with a polymer containing side chain hydroxyl groups using an acid catalyst, for example para-toluene sulfonic acid.

In addition, for polyethers having free hydroxyl groups, UV-chromophores containing hydroxyl groups can be covalently attached to the polyethers using a number of methods familiar to those skilled in the art. In one embodiment, for nucleophilic displacement, reagents such as methane sulfonyl chloride or p-toluene sulfonyl chloride can be used to activate hydroxyl groups on the UV-chromophore; The hydroxyl group on the backbone can then displace the resulting mesylate or tosylate under basic conditions to create an ether bond between the polymer and the UV-chromophore. In other embodiments, reagents such as phosgene, diphosgene, or triphosgene can be used to convert hydroxyl groups on the UV-chromophore to chloroformates; The resulting UV-chromophore chloroformate can be reacted with hydroxyl groups on the backbone of the polymer to create carbonate bonds between the polymer and the UV-chromophore. For polymers having free hydroxyl groups (as represented by structure (P _d ) in Formula VI), UV-chromophores containing amine groups can be covalently attached to the polymer using a number of methods familiar to those skilled in the art. In one embodiment, reagents such as phosgene, diphosgene, and triphosgene can be used to convert hydroxyl groups on the polymer to the corresponding chloroformates; The amine functionalized UV-chromophore can then be reacted with the polymer chloroformate to create a carbamate bond between the UV-chromophore and polyether.

In other embodiments, some of the hydroxyl groups remain on the linear polyether backbone after the acid, acid chloride, or isocyanate functional UV-chromophore is attached. These unreacted hydroxyl groups can be used to improve the physical and chemical properties of the polymer by attaching other monofunctional side groups. Examples of hydroxyl reactive functional groups include, but are not limited to, acid chloride and isocyanate. Specific examples of hydroxyl reactive functional side groups include palmitoyl chloride and stearyl isocyanate. Other examples of groups that can be pendant from polymers, sites for covalent attachment of UV-chromophores, include, but are not limited to, conjugated alkenes, amines, and carboxylic acids.

In another embodiment, the polyether backbone is a polyglycerol having a pendant hydroxyl group or a hydrophobic group, such as a polyglyceryl ester, such as the brand name polyaldo by Lonza, Allendale, N.J. (POLYALDO) Decaglyceryl monostearate sold under 10-1-S, or tetradecaglyceryl monostearate sold under the trade name PolyAl also 14-1-S by Lonza, Allendale, NJ. Pendant hydroxyl groups can be reacted with UV-chromophores containing complementary functional groups as described above to obtain UV absorbing polyethers. In this embodiment, the polymer composition will be, for example, a reaction product of a polyglycerol ester and a UV chromophore having functional groups suitable for covalent attachment to the polyglycerol ester. Suitable functional groups on the UV chromophore include carboxylates, isocyanates, especially the functional groups discussed above. The resulting polymer composition may include a linear UV absorbing polyether having repeating units shown in Formula IIB. The resulting polymer composition may further include some non-linearity (eg, cyclic component), depending on the percentage of linear material present in the polyglycerol.

Synthesis of suitable polymer compositions containing UV-absorbing polyethers, as described above, can also be achieved through polymerization of UV-chromophores covalently modified by cyclic ether groups (direct polymerization). This is illustrated in Formula VII below, where Y represents the UV-chromophore and o is the property of the ring size of the cyclic ether monomer.

Formula VII. Direct polymerization of UV-chromophores covalently attached to cyclic ethers

The polymer compositions described herein are useful for applications where UV absorption is required. For example, the polymer composition may be combined with a cosmetically acceptable carrier suitable for cosmetic applications, or by combining the polymer composition with other materials (i.e., melt blending the material with the polymer composition or coating the material with the polymer composition). It can be useful to reduce the UV degradation of a material. Incorporation of the UV-absorbing polyethers of the present invention in these compositions can provide improvements in SPF (mainly UVB absorbency), PFA (mainly UVA absorbency), or both. Cosmetically acceptable topical carriers are suitable for topical application to human skin and include, for example, one or more vehicles such as water, ethanol, isopropanol, emollients, humectants, and/or one or more. Surfactants/emulsifiers, fragrances, preservatives, waterproof polymers, and similar ingredients commonly used in cosmetic formulations. As such, the polymer composition may be formulated into a spray, lotion, gel, stick, or other product form using ingredients known in the art. Similarly, according to certain embodiments, human skin can be protected from UV radiation by topical application of a composition comprising a polymer composition containing UV-absorbing polyethers.

According to certain embodiments, sunscreen agents present in the topical compositions of the present invention may consist of or consist essentially of UV-absorbing polyethers as defined herein. According to certain other embodiments, the sunscreen agent may include additional UV-absorbing polymers and/or non-UV-absorbing, light-scattering particles other than UV-absorbing polyethers as defined herein. . Additional UV-absorbing polymers are molecules that can be shown to have one or more structural units that are periodically repeated (e.g., two or more times) to produce a molecule, as defined and claimed herein. UV-absorbing polyethers other than those used in the composition. In certain embodiments, the composition may be substantially free of UV-absorbing polymers other than UV-absorbing polyethers. In another embodiment, the composition may be substantially free of both UV-absorbing polymers other than UV-absorbing polyethers and non-polymeric UV-absorbing sunscreens (described below).

The molecular weight of the additional UV-absorbing polymer can be greater than about 1500. Examples of suitable additional UV-absorbing polymers include benzylidene malonate silicones including those described in US Pat. No. 6,193,959 (Bernasconi et al.). Particularly suitable benzylidene malonates include "Parsol SLX" commercially available from DSM (Royal DSM N.V.), Herlen, The Netherlands. Other suitable additional UV-absorbing polymers are described in US Pat. No. 6,962,692; U.S. Patent No. 6,899, 866; And/or US Pat. No. 6,800,274; Polymer with hexanedioic acid, 2,2-dimethyl-1,3-propanediol, sold under the trade name "POLYCRYLENE", available from the HallStar Company, Chicago, Illinois , 3-[(2-cyano-1-oxo-3,3-diphenyl-2-propenyl)oxy]-2,2-dimethylpropyl 2-octyldodecyl ester. These additional UV-absorbing polymers, when used, can be used at a concentration of at least about 1%, for example at least about 3%.

Non-UV-absorbing, light-scattering particles do not absorb within the UV spectrum, but can improve SPF by scattering incident UV radiation. Examples of non-UV-absorbing, light-scattering particles include solid particles having dimensions, for example, an average diameter of from about 0.1 microns to about 10 microns. In certain embodiments, the non-UV-absorbing, light-scattering particles are hollow particles consisting essentially of or comprising an organic polymer or glass. Suitable organic polymers include acrylic polymers, including acrylic/styrene copolymers, such as those known as SUNSPHERES, commercially available from Dow Chemical, Midland, Michigan. Suitable glasses include those described in published U.S. Patent Application No. Borosilicate glass is included.

Topical composition

In one embodiment, a composition suitable for topical/cosmetic use for application to a human body, for example, a keratinous surface, such as skin, hair, lips, or nails, especially the skin, is provided. The composition includes a polymer composition comprising at least one linear UV-absorbing polyether comprising a chemically bound UV-chromophore.

As discussed above, the concentration of the UV-absorbing polyether in the topical composition is about, particularly in the absence or substantial absence of additional UV-absorbing polymers or non-polymeric UV-absorbing sunscreen agents as described herein. It may be sufficient to provide an SPF of 10 or higher. Accordingly, the concentration of ultraviolet radiation absorbing polyether can vary from about 5% to about 50% of the topical composition, for example from about 7% to about 40%, for example from about 10% to about 25%. In certain embodiments, the concentration of UV-absorbing polyether is at least about 10% of the composition, for example at least about 15%, for example at least about 25%. Depending on certain embodiments in which the sunscreen agent consists essentially of UV-absorbing polyethers, the concentration of UV-absorbing polyethers may be at least about 15%.

The concentration of non-UV-absorbing light-scattering particles, if present, can be at least about 1%, for example from about 1% to about 10%, for example from about 2% to about 5%. In certain embodiments where the UV-sunscreen agent further comprises a non-UV-absorbing sunscreen agent in an amount as discussed above, the SPF of the composition of the present invention may be about 20 or greater.

According to certain embodiments, the compositions of the present invention may be substantially free of non-polymeric UV-absorbing sunscreens. In this embodiment, “substantially free of non-polymeric UV-absorbing sunscreens” is greater than 2, as determined by the in vitro method described herein below in the absence of UV-absorbing polyethers. It means that it does not contain non-polymeric UV-absorbing sunscreens in an amount effective to provide a composition with an SPF of. For example, the composition of the present invention will contain about 1% or less, or about 0.5% or less of this non-polymeric UV-absorbing sunscreen agent. An example of a non-polymeric UV-absorbing sunscreen agent that is substantially not included in the composition is typically characterized by being "organic" (including or primarily containing only atoms selected from carbon, hydrogen, oxygen, and nitrogen) , There may be no repeatable units that can be defined and typically have a molecular weight of about 600 Daltons or less, for example about 500 Daltons or less, for example less than 400 Daltons. Examples of such compounds, sometimes referred to as "monomer organic UV-absorbers", include methoxycinnamate derivatives, such as octyl methoxycinnamate and isoamyl methoxycinnamate; Camphor derivatives such as 4-methyl benzylidene camphor, camphor benzalkonium methosulfate, and terephthalidene dicamphor sulfonic acid; Salicylate derivatives such as octyl salicylate, trolamine salicylate, and homosalate; Sulfonic acid derivatives such as phenylbenzimidazole sulfonic acid; Benzone derivatives such as dioxybenzone, sulfisobenzone, and oxybenzone; Benzoic acid derivatives such as aminobenzoic acid and octyldimethyl para-amino benzoic acid; Octocrylene and other β,β-diphenylacrylates; Dioctyl butamido triazone; Octyl triazone; Butyl methoxydibenzoyl methane; Drometrizole trisiloxane; And menthyl anthranilate.

Other non-polymeric UV-absorbing sunscreens that may not be substantially included in the composition include UV-absorbing particles, such as certain inorganic oxides, including titanium dioxide, zinc oxide, and certain other transition metal oxides. Can be included. These ultraviolet screening particles are typically solid particles, which are from about 0.1 micrometers to about 10 micrometers in diameter.

The composition of the present invention can be used in a variety of cosmetic applications, especially in the protection of skin from UV radiation. Thus, the composition can be made in a wide variety of delivery forms. These forms include, but are not limited to, suspensions, dispersions, solutions, or coatings on water-soluble or water-insoluble substrates (eg, substrates such as organic or inorganic powders, fibers or films). Suitable product forms include lotions, creams, gels, sticks, sprays, ointments, mousses and compacts/powders. The composition may be used for a variety of end uses, such as recreational or commercial sunscreens, moisturizers, cosmetics/make-ups, cleanser/toner, anti-aging products, or combinations thereof. have. The composition of the present invention can be prepared using methods well known by those skilled in the art of cosmetic formulation.

The composition of the present invention comprises a continuous water phase, in which a discontinuous oil phase comprising UV-absorbing polyether is homogeneously distributed. In certain embodiments, the UV-absorbing polyether is dissolved in the oil phase as opposed to being dispersed or suspended. The oil phase can again stabilize in the water phase. The oil phase may be such that it is present in discrete droplets or units having an average diameter of about 1 micrometer to about 1000 micrometers, for example about 1 micrometer to about 100 micrometers.

The relative concentrations of the water phase and oil phase can be varied. In certain embodiments, the weight percentage of the aqueous phase is about 10% to about 90%, for example about 40% to about 80%, for example 50% to about 80%; Here, the balance is an oil phase.

The percentage of water included in the composition is from about 20% to about 90%, for example from about 20% to about 80%, for example from about 30% to about 70%, for example from about 51% to about 80%, for example For example from about 51% to about 70%, for example from about 51% to about 60%.

Topical carrier

One or more UV-absorbing polymers in the composition will have an “acceptable topical carrier for cosmetics”, ie, may have other ingredients dispersed or dissolved therein and will have acceptable properties that make them safe to use topically. Can be combined with a carrier for topical use. As such, the composition can be any of a variety of functional ingredients known in the field of cosmetic chemistry, such as other ingredients commonly used in personal care compositions, among other functional ingredients, such as wetting agents, thickeners, opacifiers , Softeners (including oils and waxes) in addition to fragrances, dyes, solvents for UV-absorbing polyethers. Suitable examples of solvents for UV-absorbing polyethers include dicaprylyl carbonate, available as CETIOL CC from Cognis Corporation, Amble, PA. In order to provide pleasant aesthetic properties, in certain embodiments of the present invention, the composition is substantially free of volatile solvents, and in particular C ₁ to C ₄ alcohols such as ethanol and isopropanol.

Additionally, the composition may be essentially free of ingredients that render the composition unsuitable for topical use. As such, the composition may be essentially free of solvents such as volatile solvents, and in particular free of volatile organic solvents such as ketones, xylenes, toluene and the like.

Emulsifier

The present inventors are substantially free of non-polymeric UV-absorbing sunscreens by forming an oil-in-water (O/W) emulsion comprising a polymer composition comprising UV-absorbing polyethers and certain emulsifiers in a certain weight range. It was surprisingly found that non-UV-protected mild sunscreens could be produced. As such, the composition of the present invention comprises an O/W emulsifier component comprising at least one O/W emulsifier. "O/W emulsifier" means any of a variety of molecules suitable for emulsification of individual oil phase droplets in a continuous aqueous phase. "Low molecular weight emulsifier" means an emulsifier having a molecular weight of about 2000 Daltons or less, for example about 1000 Daltons or less. The O/W emulsifier may be able to lower the surface tension of pure deionized water to 45 dynes/cm when added to pure deionized water at a concentration of 0.5% or less O/W emulsifier at room temperature. O/W emulsifiers are sometimes characterized by a hydrophile-lipophile balance (HLB) of at least about 8, for example at least about 10.

The O/W emulsifier component includes one or more anionic emulsifiers such that the total concentration of anionic emulsifiers in the composition is about 3% or less. Examples of suitable chemical classes of anionic emulsifiers are the following parts of alkyl, aryl or alkylaryl, or acyl-modified versions: sulfates, ether sulfates, monoglyceryl ether sulfates, sulfonates, sulfosuccinates Nate, ether sulfosuccinate, sulfosuccinate amate, amidosulfosuccinate, carboxylate, amidoethercarboxylate, succinate, sarcosinate, amino acid, taurate, sulfoacetate, and phosphate. Important anionic emulsifiers are phosphate esters, for example cetyl phosphate salts, for example potassium cetyl phosphate. In certain embodiments, the concentration of the at least one anionic emulsifier is from about 0.5% to about 3% by weight of the composition, for example from about 0.6% to about 3%, for example from about 0.6% to about 2.5%. According to certain embodiments, the O/W emulsifier component consists essentially of one or more anionic emulsifiers.

According to certain embodiments, the O/W emulsifier component is essentially free of non-ionic emulsifiers having alcohol-functional groups having 14 to 22 carbon atoms in hydrocarbon chain length. Chemical classes of non-ionic emulsifiers with alcohol functionality include fatty alcohols, for example various saturated or unsaturated, linear or branched, C ₇ to C ₂₂ nonethoxylated, aliphatic alcohols, for example with single -OH groups Things can be included. Fatty alcohols can be derived from plant or animal oils with one or more pendant hydrocarbon-comprising chains. The fatty alcohol may have from 14 to about 22 carbon atoms, for example from about 16 to about 18 carbon atoms. Examples of unbranched fatty alcohols include cetyl alcohol and stearyl alcohol.

According to certain other embodiments, the O/W emulsifier component is essentially free of cationic emulsifiers, such as alkyl quaternary, benzyl quaternary salt, ester quaternary salt, ethoxylated quaternary salt, and alkyl amines.

According to certain embodiments, in addition to the anionic oil-in-water emulsifier(s) discussed above, the O/W emulsifier component may contain additional emulsifiers, such as non-ionic emulsifiers, no amphoteric functional groups, and amphoteric emulsifiers, And/or polymeric emulsifiers. Examples of suitable chemical classes of non-ionic emulsifiers include ethoxylates of amides; Polyoxyethylene derivatives of polyol esters; Non-crosslinked silicone copolymers, such as alkoxy or alkyl dimethicone copolyols, silicones with pendant hydrophilic moieties, such as linear silicones with pendant polyether groups or polyglycerin groups; And crosslinked elastomeric solid organopolysiloxanes comprising one or more hydrophilic moieties.

Examples of suitable chemical classes of amphoteric emulsifiers include alkyl betaine, amidoalkyl betaine, alkylamphoacetate; Amidoalkyl sultaine; Amphophosphate; Imidazoline phosphorylation; Carboxyalkyl alkyl polyamines; Alkylimino-dipropionate; Alkyl amphoglycinate (mono or di); Alkyl amphopropionate; N-alkyl β-aminopropionic acid; And alkylpolyamino carboxylates. Examples of suitable chemical classes of polymeric emulsifiers include acrylamidoalkyl sulfonic acid-based copolymers, for example Aristoflex® AVC and Aristoflex® HMB by Clariant Corporation; And Grantix APP by Grant Industries, Inc.

Film-forming polymer

In certain embodiments of the present invention, the composition of the present invention comprises a film-forming polymer. A “film-forming polymer” is a polymer that, when dissolved, emulsified, or dispersed in one or more diluents, spreads it onto a smooth glass with a liquid vehicle and enables the formation of a continuous or semi-continuous film when evaporating the liquid vehicle. it means. As such, rather than forming a plurality of discrete island-like structures, the polymer should be dried on the glass mainly in a continuous manner over the area where the polymer is spread. Generally, the coating formed by applying the composition to the skin according to embodiments of the invention described herein has an average thickness of less than about 100 micrometers, for example less than about 50 micrometers.

In contrast to polymeric UV-absorbing polymers, film-forming polymers generally do not absorb ultraviolet radiation and therefore do not meet the requirements for UV-absorbing polymers. Film-forming polymers are useful in the compositions of the present invention in that they can enhance the UV-blocking properties (UV-A, UV-B, or both) of the present composition and/or improve the water resistance or water resistance of the composition. can do.

Suitable film forming polymers include natural polymers such as polysaccharides or proteins and synthetic polymers such as polyesters, polyacrylics, polyurethanes, vinyl polymers, polysulfonates, polyureas, polyoxazolines, and the like. Specific examples of film-forming polymers include, for example, hydrogenated dimer dilinoleyl/dimethylcarbonate copolymers available from Cogness Corporation, Ambuler, PA, as COSMEDIA DC; Copolymers of vinylpyrrolidone and long chain a-olefins such as those available as GANEX V220 from ISP Specialty Chemicals of Wayne, NJ; Vinylpyrrolidone/tricontanyl copolymer, also available as Gannex WP660 from IPS; Water dispersible polyesters, including sulfopolyesters, such as those available as Eastman AQ 38S from Eastman Chemical. The amount of film-forming polymer present in the composition can be from about 0.1% to about 5%, or from about 0.1% to about 3%, or from about 0.1% to about 2%.

In certain embodiments, the composition comprises an emollient used for the dissolution of UV-absorbing polyethers in addition to preventing or alleviating drying and protecting the skin. Suitable emollients include mixtures of mineral oil, petrolatum, vegetable oils (e.g. triglycerides, e.g. caprylic/capric triglycerides), waxes, and other fatty esters (esters of glycerol (e.g. isopropyl palmi Tate, isopropyl myristate)), and silicone oils such as dimethicone. In certain embodiments, mixtures of triglycerides (eg, caprylic/capric triglycerides) and esters of glycols (eg, isopropyl myristate) are used to dissolve UV-absorbing polyethers. Can be.

In certain embodiments, the composition includes pigments suitable for providing color tone or hiding power. Pigments may be suitable for use in color cosmetic products comprising compositions for application to hair, nails, and/or skin, particularly the face. Tonal cosmetic compositions include, but are not limited to, foundations, concealers, primers, blushes, mascaras, eye shadows, eyeliners, lipsticks, nail polishes, and colored humectants.

Pigments suitable for providing color tone or hiding power may be composed of iron oxide including red and yellow iron oxide, titanium dioxide, ultramarine and chromium or chromium hydroxide shades, and mixtures thereof. The pigment is a lake pigment represented by D&C and FD&C blue, brown, green, orange, red, yellow, etc., precipitated on an inert binder such as an insoluble salt, e.g. organic dye, e.g. azo, indigoide, Triphenylmethane, anthraquinone, and xanthine dyes. Examples of lake pigments include Red No. 6, Red No. 7, Yellow No. 5, and Blue No. 1. The pigment can be an interfering pigment. Examples of interference pigments include mica-based, bismuth oxychloride-based, and silica-based ones, such as mica/bismuth oxychloride/iron oxide pigments commercially available as CHROMALITE pigments (BASF), commercially available flamenco (FLAMENCO) Mica/titanium dioxide/iron oxide, including titanium dioxide and/or iron oxide coated on mica, such as pigments (BASF), commercially available KTZ pigments (Kobo products), CELLINI pearl pigments (BASF) Pigments, and borosilicate-containing pigments such as REFLECKS pigments (BASF).

The composition of the present invention may further include one or more other active agent(s) for cosmetic use. A "cosmetic active agent" is a compound that has a cosmetic or therapeutic effect on the skin, for example, an agent for treating wrinkles and acne, or an agent for whitening the skin. Cosmetic actives are typically in the composition of the present invention from about 0.001% to about 20% by weight of the composition, for example from about 0.01% to about 10% by weight of the composition, for example from about 0.1% to about 5% by weight Will be present in the amount of

In certain embodiments, the composition has a pH from about 4.0 to about 8.0, for example from about 5.5 to about 7.0.

The sun protection factor (SPF) can be tested using the following in vitro SPF test method. Baseline transmittance of the PMMA plate (substrate) to which no test material was applied was measured. Test samples were prepared by providing samples of the polymer. Blends can also be tested by this method. Without any additional additives; The polymer(s) can be tested with a solvent system, or as part of a personal care composition that can include a solvent and/or additional ingredients.

Using an application density of about 32 milligrams for a 25 cm 2 substrate, rub it into a uniform thin layer using an operator's finger and dry it, so that each sample is placed on a PMMA plate (available from Helioscience, Marseille, France). Apply separately. After drying the sample for 15 minutes, a calibrated Labsphere® UV-1000S UV transmittance analyzer or Labsphere® UV-2000S UV transmittance analyzer (Labsphere, North Sutton, New Hampshire, USA) Measure absorbance using. The SPF and PFA index (based on the bioavailability index of UVA) was calculated using absorbance measurements.

SPF and PFA can be calculated using methods known in the art, and for SPF calculation, see Equation (1) below:

[Equation 1]

here,

E(λ) = erythema action spectrum

I(λ) = spectral irradiance from UV source

A0(λ) = average single wavelength absorbance of the test product layer before UV exposure

dλ = wavelength step (1 nm)

The composition of the present invention has a low tendency to stimulate. For example, stimulation can be measured using a Modified TEP TEST as described below. The lower modified TEP value of the composition tends to show less stimulation associated with it, as compared to compositions with higher modified TEP values (these compositions tend to cause higher levels of stimulation).

Applicants have recognized that the compositions of the present invention have surprisingly low altered TEP values/lower stimuli associated therewith. For example, in certain embodiments, when determined according to a modified TEP test as described below, the modified TEP value of the composition is 0.3 or less, or about 0.25 or less, or about 0.20 or less.

The compositions of the present invention can be prepared using mixing and blending methods well known by those skilled in the art. In one embodiment of the present invention, a method of preparing a composition of the present invention comprises the steps of: preparing an oil phase by mixing at least UV-absorbing polyether with any oil-soluble or oil-miscible component; And preparing an aqueous phase by mixing water with any water-soluble or water-miscible component. The oil phase and water phase can then be mixed in a manner sufficient to homogeneously disperse the oil phase in the water phase such that the water phase is continuous and the oil phase becomes discontinuous.

The composition of the present invention can be used by topical administration to a mammal, for example by placing the composition directly on human skin or hair, wiping or spreading.

The following modified TEP test is used in this method and the following examples. In particular, as described above, a modified TEP test is used to determine in which case the composition has a reduced stimulus according to the present invention.

Modified TEP test:

To assess the ability of the test material to break down the permeable barrier formed by the confluent monolayer of Madin-Darby canine kidney cells (MDCK), a modified TEP test is designed. MDCK cells grown saturated on a porous filter are used to assess trans-epithelial permeability as determined by leakage of fluorescein dye through a monolayer. Since the MDCK permeable barrier is a model for the outermost layer of the corneal epithelium, this system can be considered to reflect initial changes in the development of eye irritation in vivo.

The following equipment is suitable for the modified TEP test: Packard Multiprobe 104 Liquid handling system; BioTek Washer, model number ELx405; And BioTek Powerwave XS microplate reader with 490 nm filter. Disposable laboratory supplies include: Corning Support Transwell 24-well cell culture plates with microporous membrane, Cat. No. 29445-100 or 29444-580, MFG. No. 3397; Corning Receiver 24-well tissue culture plate, Cat No. 29444-100, MFG. No. 3527; Disposable 200 μL tip Cat. No. 82003-196; Eppendorf 5 mL Combitip Plus Cat No. 21516-152; Sodium chloride 0.9% (w/v) aqueous Cat. No. RC72105; And sterile 15 mL polypropylene centrifuge tubes. Reagents supplied by Life Technologies include: Hank's Balanced Salt Solution (10x) without phenol red. No. 14065056 and sodium bicarbonate solution, 7.5% Cat No. 25080094, Minimum Essential Medium (MEM) (1x), Cat No. 11095072, fetal calf serum, HI Cat No. 10082147, antibiotic antifungal agent 100x Cat No. 15240096, L-glutamine 200 mM (100x) Cat No. 25030081, sodium fluorescein, Sigma Cat. No. F-6377 is provided by Sigma/Aldrich.

The cell line, ATCC CCL 34 MDCK (NBL-2) (height: Canis familiaris), is maintained according to the recommendation of ATCC (Manassas, Va.). Cell cultures are harvested by trypsin treatment and inoculated into support transwell 24 plates containing complete MEM and tested at a concentration of 5x10 ⁵ cells/mL after 48 hours. Reagents are prepared as follows: (1) 200 mL of Hank Equilibrium Salt Solution (HBSS) (10x) without phenol red is combined with 9.3 mL of sodium bicarbonate and the volume is increased to 2000 mL with distilled water. 1X HBSS buffer. The pH should be in the range of 6.8 to 7.2 and the solution should be warmed to 37 C; (2) 200 ug/mL stock solution of sodium fluorescein in HBSS buffer; (3) Complete minimal essential medium (MEM) is prepared by combining 100 mL of fetal bovine serum, 10 mL of antibiotic antifungal agent 100x, and 10 mL of L-glutamine 200 mM (100x) into 1000 mL of MEM (1x). .

The permeability of the membrane is confirmed by including a cell-free control run with the test of each day. The sunscreen test composition is evaluated for full strength.

Cell media is removed by washing the insert. A 24-well cell culture plate containing a saturated monolayer of MDCK cells, Corning Cat No.29445-100 is removed from the incubator. Each 24-well cell culture plate includes an insert that secures an inner well with a microporous membrane cell growth surface suspended into a sub well. The insert containing the cell culture is washed 5X (Biotech Washer) with warm HBSS to remove the culture medium and serum. The bottom of the 24-well cell culture plate is washed 3X with warm HBSS and 1 mL of HBSS is dispensed into each bottom well at the final wash.

Since 4 wells in 24-well plates per sunscreen test composition are used, up to 6 sunscreen test compositions can be tested using a single 24-well plate. The sunscreen test composition is added directly to the insert well (knit (100%), 200 μL/insert well). The 24-well cell culture plate is then returned to the incubator for a 1 hour incubation period.

Upon completion of the first incubation step, the 24-well cell culture plate is removed from the incubator and manually washed to remove the test composition. Approximately 200 μL of HBSS is added to each inner well and soaked for approximately 1 minute. The test composition and HBSS are then decanted from individual wells. Any residual sample is removed by delicately flooding and pouring the insert with HBSS. When there is no residual test composition in the insert, a 10X wash (Biotech Washer) should be run with warm HBSS. The bottom wells are washed 3X with warm HBSS and 1 mL of HBSS (receiver buffer) is dispensed into each bottom well at the final wash.

Insert the insert back into the bottom plate containing 1 mL HBSS (receiver buffer), add sodium fluorescein to each inner well (200 μL/well), and return the plate to the incubator for a period of 45 minutes.

After a 45 minute incubation, the first plate containing sodium fluorescein is removed from the incubator, the upper insert is removed, and the amount of dye leaked into the receiver buffer in the lower well is determined by a Powerwave XS microplate reader. Fluorescence is read spectrophotometrically at 490 nm. Print and record data.

The insert is then placed in an empty temporary 24-well bottom plate on a Biotech washer for 10X HBSS cleaning. Care should be taken to ensure that sodium fluorescein has been washed and that there is no residual fluorescein in the top (inside) or bottom well.

Washed inserts in new 24-well receiver cell culture plates, Corning Cat No. Add to 29445-100. Both the inner well and the bottom plate of the insert are completely minimal essential media (MEM), Life Technologies, Cat No. Accommodates 11095072 Approximately 1 mL of complete MEM is added to the bottom well and 200 μL is added to the inner well. The 24-well cell culture plate is then incubated for 3 hours.

After a 3 hour incubation, 24-well cell culture plates are removed from the incubator. The insert containing the cell culture is washed 5X (Biotech Washer) with warm HBSS to remove the culture medium and serum. The bottom plate is washed 3X with warm HBSS and 1 mL of HBSS is dispensed into each bottom well at the final wash (receiver buffer).

Sodium fluorescein is added to each inner insert well (200 μL/well) and the plate is reassembled and returned to the incubator for a period of 45 minutes.

After a 45 minute incubation, the plate containing sodium fluorescein is removed from the incubator, the insert is removed and discarded, and the amount of dye leaked into the lower well is determined by a Powerwave XS microplate reader. Fluorescence is read spectrophotometrically at 490 nm. Print and record data.

The average fluorescein leak value for the sunscreen test composition is calculated using the spectrophotometric measurements (fluorescein leak) for each of the 4 iterations of a given sunscreen test composition. The average fluorescein leak value of the four “cell-free control” wells is also calculated. The modified TEP score is calculated by dividing the mean fluorescein leakage value of the sunscreen test composition by that of a cell-free control.

Additional details of the TEP test are described in the following publication: Tchao, R. (1988) Trans-epithelial Permeability of Fluorescein In Vitro as an Assay to Determine Eye Irritants. Alternative Methods in Toxicology 6, Progress in In Vitro Toxicology (ed. AM Goldberg), 271].

The following examples illustrate, but are not limited to, the principles and practice of the present invention. Many additional embodiments will become apparent to those skilled in the art once within the scope and spirit of the invention once they have the advantage of this disclosure.

Example

Examples 1 to 12: Synthesis and SPF test of polymer composition comprising UV-absorbing polyether

Example 1. Synthesis of glycidol in protected form.

Formula VIII. Synthesis of protected epoxide monomer

Synthesis of the protected epoxide monomer (1) was performed, as illustrated in Formula VIII, using a modification of the procedure described in Fitton, A. et. al. Synthesis 1987, 1987 , 1140-1142. Glycidol (53 mL, 0.80 mol) and ethyl vinyl ether (230 mL, 2.40 mol; distilled just before reaction) were added to a two-neck 500 mL round-bottom flask with a magnetic stir bar. The flask was fitted with a septum and thermometer adapter; The thermometer was inserted into the adapter and placed so that the bulb was submerged in the liquid. Soak the flask in a brine/ice bath; The mixture was magnetically stirred. When the internal temperature was 0°C, p-toluene sulfonic acid hydrate (pTSA.H ₂ O, 1.43 g, 7.5 mmol) was added in small portions with vigorous stirring. When each portion of pTSA was added, the temperature of the solution increased rapidly; The rate of addition was slow enough to prevent the solution temperature from increasing above 20°C. The final portion of pTSA was added ~5 hours after the addition of the starting portion and did not cause fever; Thin layer chromatography of the reaction mixture showed no residual glycidol after the final pTSA addition, the reaction mixture was transferred to a separatory funnel; Saturated aqueous NaHCO ₃ (230 mL) was poured slowly into the funnel. The mixture was shaken, the layers were separated, the organic layer was removed, dried over sodium sulfate and filtered through paper. The solution was concentrated by rotary evaporation, followed by vacuum distillation (distillate at 60° C. at 8 Torr) to afford the protected epoxide monomer (1) (79.38 g) as a clear oil. NMR analysis was performed at 30° C. on a Varian Unity Inova 400 MHz spectrometer, ( ¹ H) spectrometer; Chemical shifts were reported in parts per million (ppm) on the δ scale and were based on residual protonated solvent peaks or tetramethylsilane. The spectrum obtained from DMSO- d ₆ was based on (C H D ₂ )(CD ₃ )SO of δ _H 2.50. ¹ H NMR (400 ㎒, CDCl ₃ ) δ ppm 4.76 (quin, J =5.2 ㎐, 1 H), 3.81 (dd, J =11.5, 3.3 ㎐, 1 H), 3.60-3.74 (m, 3 H), 3.38-3.60 (m, 4 H), 3.10-3.20 (m, 2 H), 2.81 (ddd, J =5.1, 4.0, 1.3 ㎐, 2 H), 2.63 (ddd, J =14.6, 5.1, 2.7 ㎐, 2 H), 1.33 (dd, J =6.2, 5.4 ㎐, 6 H), 1.21 (td, J =7.1, 1.3 ㎐, 6 H).

Example 2A. Synthesis of linear polyglycerol

Formula IX. Synthesis of linear polyether polymers

Polymerization of the protected epoxide monomer (1) was accomplished as illustrated in Formula IX. 1-Octadecanol (27.76 g, 102.6 mmol) was added to an oven dried 250 mL two neck round bottom flask with a magnetic stir bar. The flask was equipped with a nitrogen inlet adapter and a rubber septum. Potassium methoxide (25 wt% in methanol (MeOH), 6.06 mL, 20.52 mmol) was added to the flask through the septum with a syringe. The round bottom flask was immersed in an oil bath preheated to 90°C. The septum was pierced with an 18 gauge needle, and the material in the flask was stirred for 1 hour under a constant stream of nitrogen gas, during which time the alcohol melted and methanol was evaporated from the flask. The diaphragm was replaced with a pressure equalizing addition funnel containing monomer (1) (151 g, 1.04 mol). The funnel was sealed with a rubber septum. Monomer (1) was added dropwise to the stirred mixture; The reaction mixture was stirred at 90° for 15 hours. Upon cooling, crude polyether (2) was obtained as a pale brown, slightly viscous oil, which was used in the subsequent reaction without further purification. ¹ H NMR (400 ㎒, chloroform- d ) δ ppm 4.48-4.80 (m, 10 H), 3.25-3.97 (m, 70 H), 1.41-1.64 (m, 2 H), 1.23-1.40 (m, 60 H), 1.09-1.23 (m, 30 H), 0.88 (t, J =7.0 ㎐, 3 H).

Gel permeation chromatography for molecular weight determination at 35° C. at a flow rate of 0.5 mL/min THF (stabilized with 0.025% BHT) in a Waters Alliance 2695 separation module (Waters, Milford, Mass.) Was performed. Two GPC columns in series (Waters Corp HR 0.5 and HR3 with dimensions of 7.8×300 mm and particle size of 5 μm) and a Waters Model 410 refractive index detector were mounted on the 2695. The molecular weight of the sample was determined compared to the polystyrene standard. Standards were prepared by weighing 1 to 2 mg of each polystyrene (PS) polymer and placing them in 2 mL vials containing THF solvent (two standards per vial); Samples were filtered before analysis (0.22 μm). Polystyrene standards ranged from 70,000 to 600 Daltons, and were manufactured by three suppliers (Polymer Standards Service-USA, Phenomenex, and Shodex). The resulting calibration curve gave r ² = 0.9999. Experimental samples were dissolved in THF at a concentration of 3 to 5 mg/mL and filtered (0.22 μm) before analysis. GPC (THF) analysis for polymer (2): M _w 1724.

The crude polyether (2) with tetrahydrofuran (THF, ˜500 mL) was transferred to a 1 L round bottom flask with a magnetic stir bar. Concentrated HCl aqueous solution (37%, 20 mL) was added to the stirred reaction mixture with a glass pipette. After 16 hours, the reaction mixture was concentrated to oil by rotary evaporation, which was diluted to about 500 mL with methanol. Solid NaHCO ₃ was added in portions to the vigorously stirred solution, which caused significant bubbling. When the addition of NaHCO ₃ did not produce additional bubbling (total NaHCO ₃ added was 107 g), the mixture was filtered through paper to remove solid NaHCO ₃ . The filtrate was concentrated by rotary evaporation to give linear polyglycerol (3) as a tan foam. ¹ H NMR (400 ㎒, DMSO- d ₆ ) δ ppm 4.43 (br.s., 11 H), 3.20-3.70 (m, 52 H), 1.38-1.55 (m, 2 H), 1.23 (s, 30 H), 0.85 (t, J =7.0 kPa, 3 H).

Example 2B. Synthesis of linear polyglycerol.

Different batches of protected crude polymer 2 (260 g) and methanol (ACS grade, 1.25 L) were transferred to a 2 L 2-neck round bottom flask. Dry, H ⁺ form acidic ion exchange resin (Dowex DR-2030 from Aldrich, 446483; 100.3 g) was added to the flask. The middle hole of the flask was equipped with an adapter and paddle for mechanical stirring; A water-cooled distillation adapter was attached to the side hole of the flask. The reaction flask was immersed in an oil bath. With vigorous mechanical stirring, the reaction mixture was heated to boiling (oil bath temperature 85° C.). Methanol (and methyl ether resulting from removal of the protecting group) was distilled from the flask. After 750 mL of methanol was collected, an additional portion of methanol (750 mL) was added to the reaction mixture. An additional 750 mL of methanol was allowed to distill from the flask. Decolorizing charcoal was added to the hot reaction mixture. The mixture was stirred briefly and then filtered through paper. The filtrate was concentrated by rotary evaporation. The residual solvent was removed under vacuum to give the final linear polyglycerol as a yellowish foam (107 g).

Example 3A. Synthesis of benzotriazole chromophore carboxylate.

Formula X. Benzotriazole carboxylate.

Polyethylene glycol ester of 3-[3-(2H-1,2,3-benzotriazole-2-yl)-5- tert -butyl-4-hydroxyphenyl]propanoate (Wyandotte, Michigan, USA) A chromophore sold under the trade name Tinuvin 213 by BASF Corporation (81.0 g) was added to a 2 L round bottom flask with a magnetic stir bar. EtOH (600 mL) was added to the flask by funnel, and the mixture was stirred until homogeneous. Sodium hydroxide (NaOH, 30.8 g) was dissolved in H ₂ O (400 mL); The basic solution was transferred to an addition funnel on a 2L flask. NaOH solution was slowly added to the stirred mixture; The pale amber, turbid solution immediately turned clear and dark orange. When the addition was complete, the mixture was stirred overnight at room temperature. The solution was concentrated by rotary evaporation to remove most of the EtOH. The resulting orange oil was diluted to 1400 mL with H ₂ O. The mixture was mechanically stirred and acidified to about pH 1 by adding 1 M aqueous HCl solution (about 700 mL). The resulting white precipitate was filtered and squeezed to remove water, then recrystallized from EtOH. The first crop crystals were long, thin, colorless needles. The supernatant was removed and concentrated by rotary evaporation; The second crop material was isolated as a white, amorphous solid. The two harvests were combined and dried in a vacuum oven overnight to give a UV-chromophore having carboxylate groups, specifically benzotriazole carboxylate (4), 3-(3-(2H-benzo[d][1,2,3) ] Triazole-2-yl)-5-(tert-butyl)-4-hydroxyphenyl) propanoic acid (37.2 g) was obtained as a white solid; Its structure is illustrated in Formula X. ¹ H NMR (400 ㎒, DMSO- d ₆ ) δ ppm 11.25 (br. s, 1 H), 8.00-8.20 (m, 2 H), 7.95 (d, J = 2.1 ㎐, 1 H), 7.50-7.67 (m, 2 H), 7.28 (d, J = 2.1 ㎐, 1 H), 2.87 (t, J = 7.5 ㎐, 2 H), 2.56 (t, J = 7.5 ㎐, 2 H), 1.45 (s, 9 H).

Example 3B. Synthesis of benzotriazole chromophore carboxylate.

Benzenepropanoic acid, 3-(2H-benzotriazole-2-yl)-5-(1,1-dimethylethyl)-4-hydroxy-, C7-9-branched and linear alkyl ester (Ti from BASF Nubin 99, commercially available; 120 g, 265.7 mmol) was added to a 3 L 1-neck round bottom flask containing a magnetic stir bar. Isopropanol (900 ml, ACS grade) was added to the flask and the resulting mixture was stirred until completely dissolved. Sodium hydroxide (36 g, 900 mmol) was dissolved in 600 ml of distilled water and the solution was added to the reaction mixture. The resulting opaque mixture (which becomes a clear orange solution after 40 min) is stirred for 24 hours at room temperature, then slowly added to a vigorously stirred mixture of isopropanol (1800 ml, ACS grade) and 1N HCl (1200 ml). It was added and cooled to 10-15°C. The precipitated white solid was filtered, washed with 1.2 L of a 1:1 isopropanol-1N HCl mixture, suspended in 2 L of 0.25 N HCl, stirred for 1 hour, filtered and filtered at 90° C. overnight in a vacuum oven. It was dried. The resulting UV-chromophore having a carboxylate group, specifically benzotriazole carboxylate (4) (37.2 g), was obtained as a pale yellow solid (85 g, 94.5%).

Example 4. Esterification of a polyether skeleton with benzotriazole carboxylate.

Formula XI. Esterification of polyglycerol and benzotriazole carboxylate

Formula XI illustrates the esterification of polyglycerol (3) with benzotriazole carboxylate (4) using catalytic tin. The linear polyglycerol (3) of Example 2A (5.52 g, 60.1 hydroxyl milliequivalents) was dissolved in methanol and transferred to a 500 mL 2-neck round bottom flask. Methanol was removed using rotary evaporation; Benzotriazole carboxylate (4) (20.38 g, 60.1 mmol) and a magnetic stir bar were added to the flask. The flask was equipped with a vacuum distillation adapter with a 100 mL collection flask and a nitrogen inlet adapter. The flask was placed under vacuum (<1 Torr) for 1 hour, then backfilled with nitrogen gas. The inlet adapter was removed from the 500 mL flask; Tin(II) ethyl hexanoate (49 μL, 0.15 mmol) was added to the flask by syringe under a stream of nitrogen. The device was reassembled and immersed in an oil bath preheated to 200°C. When most of the solids melted, the oil bath was cooled to 190°C. The reaction mixture was stirred for 16 hours under nitrogen flow. While maintaining temperature and stirring, the reaction flask was then placed under vacuum (<1 Torr) for an additional 24 hours. The device was then backfilled with nitrogen and cooled to room temperature. The material was freeze fractured and ground into powder using a pestle and pestle. The powder was dissolved in a minimal amount of THF. Methanol (900 mL) and magnetic stir bar were added to the Erlenmeyer flask; The flask was immersed in an ice bath. THF solution was added to methanol with vigorous stirring; The resulting precipitate was isolated by vacuum filtration. The residual solvent was removed under vacuum overnight to give linear polyglycerol (5) (18.7 g) as an off-white solid. ¹ H NMR (400 ㎒, CDCl ₃ ) δ ppm 11.71 (br.s., 9 H), 8.03 (br.s., 9 H), 7.80 (br.s, 18 H), 7.28-7.48 (m, 18 H), 7.12 (br. s, 9 H), 5.19 (br. s, 1 H), 3.98-4.46 (br. m, 20 H), 3.21-3.61 (br. m, 32 H), 2.91 ( br.s, 18 H), 2.67 (br.s, 18 H), 1.38-1.51 (m, 85 H), 1.13-1.35 (m, 28 H), 0.87 (t, J =6.6 ㎐, 3 H) . GPC (THF): M _w 3299; M _n 2913.

Example 5. Acid chloride of benzotriazole carboxylate (3-(3-(2H-benzo[ d ][1,2,3]triazole-2-yl)-5-( tert -butyl)-4 -Hydroxyphenyl)propanoyl chloride).

Formula XII. Conversion of benzotriazole carboxylate to benzotriazole acid chloride

The conversion of benzotriazole carboxylic acid (4) to the corresponding benzotriazole acid chloride (6) is illustrated in Formula XII. Benzotriazole carboxylate (4) (50 g 147 mmol) synthesized as described in Example 3 was added to a 1,000 mL three-necked flask with a magnetic stir bar; The flask was equipped with a reflux condenser, nitrogen inlet, and rubber septum. Anhydrous toluene (approximately 500 mL) was transferred by cannula through the septum to the flask. Thionyl chloride (16.1 mL, 221 mmol) was transferred to the flask by syringe; Dimethylformamide (2.7 mL) was then added to the flask by syringe. The flask was immersed in an oil bath set at 80°C; The suspension was stirred; The solid started to disperse, eventually giving a clear solution. After about 4 hours, the reaction mixture was allowed to cool, transferred to a round-bottom flask and concentrated by rotary evaporation. The resulting oil was triturated with hexane to give a beige solid. The suspension of material was recrystallized by adding additional hexane and warming to reflux, filtering through paper and slowly cooling to room temperature with stirring. The resulting beige crystals were filtered and dried under vacuum at 50°C. The filtrate was concentrated and recrystallization was performed again to obtain a second crop of crystals again; The combined harvest mass of benzotriazole acid chloride (6) was 44.7 grams. ¹ H NMR (400 ㎒, CDCl ₃ ) δ 11.88 (s, 1 H), 8.16 (d, J = 2.2 ㎐, 1 H), 7.91-7.98 (m, 2 H), 7.47-7.54 (m, 2 H ), 7.21 (d, J = 2.2 ㎐, 1 H), 3.29 (t, J = 7.5 ㎐, 2 H), 3.07 (t, J = 7.5 ㎐, 2 H), 1.50-1.53 (s, 9 H) .

Example 6. Isocyanates of benzotriazole acid chloride (2-(2H-benzo[d][1,2,3]triazole-2-yl)-6-(tert-butyl)-4-(2- Conversion to isocyanatoethyl)phenol).

Formula XIII. Conversion of acid chloride to isocyanate

The synthesis of benzotriazole isocyanate 7 suitable for coupling to pendant functional groups is illustrated in Formula XIII. Sodium azide (NaN ₃ , 2.5 g, 38 mmol: CAUTION! NaN ₃ is a violent poison) was carefully transferred to a 1-neck 500 mL round bottom flask with a magnetic stir bar. Deionized water (20 mL) was added to the flask; NaN ₃ was dissolved while mixing to obtain a clear solution. The flask was immersed in an ice bath. Acid chloride (6) (7.0 g 20 mmol) and anhydrous acetone (45 mL) were transferred to a funnel addition funnel in a positive pressure N ₂ atmosphere glove box. Acid chloride was dissolved in acetone while stirring gently to obtain a clear yellow solution. An addition funnel containing benzotriazole acid chloride (6) was mounted in a flask containing an aqueous solution of NaN ₃ ; An N ₂ adapter connected to the vacuum gas manifold was mounted on top of the addition funnel. A solution of benzotriazole acid chloride (6) was added dropwise to the NaN ₃ solution. After adding a few drops, a white precipitate began to appear and was suspended in aqueous solution. The addition of benzotriazole acid chloride (6) was completed within 30 minutes; Mixing was continued for 20 minutes in an ice bath. Water (30 mL) was added to the resulting white slurry; The solid was collected by filtration through a glass frit funnel under vacuum. The white solid was transferred to a separatory funnel followed by CHCl ₃ (185 mL). The flask was shaken and the layers were allowed to separate. The lower organic phase was removed from a small amount of aqueous layer and dried over Na ₂ SO ₄ . The solution was filtered; The filtrate was placed in a 1-neck 500 mL round-bottom flask containing a magnetic stir bar; The flask was equipped with a reflux condenser with nitrogen inlet adapter, and the flask was immersed in an oil bath. The solution was heated to reflux slowly over 30 minutes. The final oil bath temperature was 65°C. As the oil bath temperature exceeded 55°C, bubble generation in the solution became apparent. The reaction was left to reflux for a total of 90 minutes. CHCl ₃ was then removed by rotary evaporation; The resulting oil was left to stand overnight to crystallize to give benzotriazole isocyanate (7) (5.8 g) as a slightly gray solid. ¹ H NMR (400 ㎒, CDCl ₃ ) δ 11.91 (s, 1 H), 8.18 (d, J =1.9 ㎐, 1 H), 7.92-7.98 (m, 2 H), 7.47-7.53 (m, 2 H ), 7.23 (d, J =2.1 ㎐, 1 H), 3.59 (t, J =6.9 ㎐, 2 H), 2.96 (t, J =6.9 ㎐, 2 H), 1.52 (s, 9 H).

Example 7. Coupling of isocyanates to polyglycerol.

Formula XIV. Reaction of polyglycerol and isocyanate

The reaction of linear polyglycerol (3) with benzotriazole isocyanate (7) is illustrated in Formula XIV.

The solution of polyglycerol (3) in methanol is concentrated by rotary evaporation; The residual solvent was removed at 75° C. overnight in a vacuum oven. To a 100 mL 2-neck round bottom flask with a magnetic stir bar was added polymer (2.22 g, 24.1 hydroxyl milliequivalents). Isocyanate 7 (7.65 g, 22.7 mmol), bismuth catalyst (25 mg; bismuth carboxylate complex sold under the trade name BICAT 8210 by Shepherd Chemical, Norwood, Ohio, USA) and THF (17.4 ml, dried through 3 angstrom molecular sieve) was added to the flask. The flask was placed in an oil bath heated to 65°C, and a gas inlet was fitted. The reaction mixture was stirred under a nitrogen atmosphere for 5 hours, then allowed to cool to room temperature. FTIR was used to confirm the disappearance of the strong isocyanate peak at 2250 cm ^-1 . The reaction mixture was poured into 160 ml of methanol, producing a tan precipitate. The methanol was decanted and the product was washed with methanol (2 x 75 mL) in the flask. Remove the residual solvent at 60° C. overnight in a vacuum oven; The material was ground into a fine powder.

Example 8. Synthesis of epoxide chromophore for direct polymerization method.

Formula XV. Synthesis of epoxide chromophore monomer

The synthesis of epoxide monomer 9 with a benzotriazole chromophore is illustrated in Formula XV. Transfer a solution of lithium aluminum hydride (LAH) in THF (1 M, 250 mL) into a oven-dried 500 mL two-neck round-bottom flask with a magnetic stir bar under a nitrogen atmosphere, and add a rubber septum and equalization funnel to the flask. Was mounted. The reaction flask was immersed in an ice bath; Stirring was started. Benzenopropanoic acid, 3-(2H-benzotriazol-2-yl)-5-(1,1-dimethylethyl)-4-hydroxy, containing 5% by weight 1-methoxy-2-propyl acetate ,C7 to C9 branched and linear alkyl esters (50.06 g; benzotriazole UV absorbing product sold under the trade name Tinuvin 99-2 by BASF Corporation, Wyandotte, Michigan), to an addition funnel, THF anhydrous (30 mL). THF solution containing benzotriazole was added dropwise to the solution containing LAH; The result was a slow fizzing. After completion of the addition, an additional portion of LAH solution (100 mL) was added to the reaction flask by cannula. The reaction was allowed to warm to room temperature while stirring. After 2 hours, the reaction mixture was poured into a 1 liter Erlenmeyer flask in an ice bath. Water (approximately 60 mL) was added slowly to mechanically stir the solution while quenching any residual LAH (Extremely Note: Quenching LAH with water is exothermic and releases a large amount of extremely flammable H ₂ gas) . When LAH was quenched (no additional gas was released by the addition of water), the gray suspension was diluted to 1 L using a 1 M aqueous HCl solution. The solution was transferred to a 2 L separatory funnel and extracted with ethyl acetate (1×400 mL, then 2×50 mL). The combined ethyl acetate layers were washed with brine (1×400 mL), dried over Na ₂ SO ₄ and then filtered through paper. The solvent was first removed by rotary evaporation and then removed in a vacuum oven overnight to give benzotriazole alcohol (8) (42.16 g) as a beige solid with a strong unpleasant odor. ¹ H NMR (400 ㎒, CDCl ₃ ) δ ppm 11.75 (s, 1 H), 8.15 (d, J =2.1 ㎐, 1 H), 7.88-7.99 (m, 2 H), 7.43-7.52 (m, 2 H), 7.22 (d, J =2.1 ㎐, 1 H), 3.75 (m, 2 H), 3.62 (br.s, 1 H), 2.77 (t, J =7.7 ㎐, 2 H), 1.91-2.06 (m, 2 H), 1.52 (s, 9 H).

Sodium hydride (6.0 g, 250 mmol) was added to an oven dried 3-neck round bottom flask with a magnetic stir bar. The flask was equipped with an equalizing funnel, nitrogen inlet adapter and rubber septum. Dry THF (300 mL) was added to the flask by cannula under nitrogen; The flask was then immersed in an ice bath and stirring was started. Benzotriazole alcohol (8) (20.0 g, 61.5 mmol) and a small magnetic stir bar were added to the addition funnel; THF was added to the addition funnel with a cannula and the stirring bar was rotated to promote dissolution of the alcohol in THF. The final volume of the alcohol/THF solution was 65 mL. This solution was added dropwise to a cold, stirred sodium hydride suspension. The cold reaction mixture was stirred for 1 hour, then epichlorohydrin (20 mL, 256 mmol) was added via a septum with a syringe. The addition funnel was replaced with a reflux condenser with a nitrogen inlet and a round bottom flask was immersed in an oil bath at 70°C. After the mixture was stirred for 19 hours, the mixture was transferred to a separatory funnel with 1 M aqueous HCl (750 mL) and ethyl acetate (500 mL). After shaking, the aqueous layer was decanted. The organic layer was washed with water (2×250 mL) and brine (1×250 mL) and then dried over Na ₂ SO ₄ . The solution was concentrated by rotary evaporation. The crude product was purified by chromatography on silica gel (6:1 hexane/ethyl acetate). Fractions containing the desired product were pooled and concentrated by rotary evaporation; The residual solvent was removed under vacuum overnight to give an epoxide monomer (9) (7.35 g) with a benzotriazole chromophore as a beige solid. ¹ H NMR (400 ㎒, CDCl ₃ ) δ ppm 11.77 (s, 1 H), 8.14 (d, J =1.9 ㎐, 1 H), 7.85-8.00 (m, 2 H), 7.41-7.53 (m, 2 H), 7.21 (d, J =1.9 ㎐, 1 H), 3.74 (dd, J =11.5, 3.1 ㎐, 1 H), 3.57 (ddt, J =19.8, 9.3, 6.4 ㎐, 2 H), 3.43 ( dd, J =11.5, 5.8 ㎐, 1 H), 3.19 (ddt, J =5.8, 4.0, 2.9 ㎐, 1 H), 2.82 (br. t, J =4.7 ㎐, 1 H), 2.76 (br. t , J =7.7 ㎐, 2 H), 2.64 (dd, J =5.1, 2.6 ㎐, 1 H), 1.93-2.04 (m, 2 H), 1.52 (s, 9 H).

Example 9. Esterification of alternative polyglycerol with benzotriazole acid.

Polyglycerol partially esterified with stearic acid (2.5 g, 19.8 hydroxy milliequivalents; tetradecaglyceryl monostearate sold under the trade name Polyaldo 14-1-S by Lonza, Allendale, NJ), and The benzotriazole carboxylate (4) (8.8 g, 23.8 mmol) was transferred to a two-neck 100 mL round bottom flask with a magnetic stir bar. The flask was equipped with a distillation adapter with a 100 mL collection flask and a nitrogen inlet adapter. The device was left under vacuum for 1 hour, then backfilled with nitrogen. The distillation head was removed and tin(II) ethyl hexanoate (50 μL) was added to the reaction flask by syringe under nitrogen flow. The device was reassembled, then purged under nitrogen with 3 times and backfilled. The reaction flask was immersed in an oil bath heated to 180° C., and a constant flow of nitrogen was introduced into the two-necked flask through a distillation adapter to exit the vacuum adapter into an indoor atmosphere. The reaction was stirred for 3 hours and then cooled to room temperature under nitrogen flow to give the product UV absorbing polyglycerol as a yellow solid. ¹ H NMR (400 ㎒, CDCl ₃ ) δ ppm 11.81 (br.s., 2 H), 8.15 (br.s., 2 H), 7.75-8.02 (br.s, 4 H), 7.34-7.58 ( br.s, 4 H), 7.21 (br.s., 2 H), 4.93-5.32 (br, 1 H), 3.17-4.50 (br. m, 38 H), 2.86-3.11 (br. m, 4 H), 2.54-2.84 (br. m, 4 H), 2.31 (br.s., 2 H), 1.61 (br.s., 2 H), 1.50 (br.s., 18 H), 1.26 ( br. s., 28 H), 0.89 (t, J =6.3 kPa, 3 H). GPC (THF): M _w 1700; M _n 950.

Example 10. Synthesis of benzotriazole acid methyl ester.

Formula XVI. Synthesis of methyl ester (11)

The synthesis of benzotriazole methyl ester (11) intended for transesterification with a polymer having hydroxyl functionality is illustrated in Formula XVI. Beta-[3-(2-H-benzotriazole-2-yl)-4-hydroxy-5- tert -butylphenyl]-propionic acid-poly(ethylene glycol) 300-ester (50.1 g; with Michigan, USA A UV absorbing product sold under the trade name Tinuvin 1130 by BASF Corporation of Eondot) was added to a two-neck, one-liter round-bottom flask with a magnetic stir bar. Methanol (500 mL) was added to the flask. Dipping the flask in an oil bath; The solution was stirred. p-TSA.H ₂ O (0.63 g) was added to the solution. The two-necked flask was equipped with a reflux condenser and a rubber septum; The oil bath was warmed to reflux the stirred reaction mixture; Reflux was maintained for 17 hours. The flask was then removed from the oil bath and allowed to cool to room temperature, at which time the product precipitated as a white solid. The precipitate was isolated by vacuum filtration, and then recrystallized from methanol; The solid was isolated by vacuum filtration and dried under vacuum at 80° C. to give benzotriazole methyl ester (11) (18.27 g) as a white solid. ¹ H NMR (400 ㎒, CDCl ₃ ) δ ppm 11.81 (s, 1 H), 8.16 (d, J =2.1 ㎐, 1 H), 7.90-7.98 (m, 2 H), 7.45-7.53 (m, 2 H), 7.22 (d, J =2.2 ㎐, 1 H), 3.71 (s, 3 H), 3.01 (t, J =7.8 ㎐, 2 H), 2.71 (t, J =7.8 ㎐, 2 H), 1.51 (s, 9 H).

Example 11. Ester exchange of benzotriazole methyl ester and polyglycerol polymer.

Formula XVII. Ester exchange with polyglycerol

The transesterification of benzotriazole methyl ester (11) and polyglycerol (3) is illustrated in Formula XVII. The solution of the solution of polyglycerol (3) in MeOH is concentrated by rotary evaporation; Residual solvent was removed under vacuum at 75° C. overnight. To a 100 mL 2-neck round bottom flask with a magnetic stir bar was added polyglycerol (3) (1.36 g, 14.9 hydroxyl milliequivalents). Benzotriazole methyl ester (11) (4.24 g, 12 mmol) and pTSA.H ₂ O (7.1 mg) were added to the flask. The flask was equipped with a distillation adapter with a 100 mL collection flask and a nitrogen inlet adapter. The reaction flask was immersed in an oil bath, and the oil bath was warmed to 175°C. Within 20 minutes, all of the reactants melted. The reaction mixture was stirred vigorously under a stream of nitrogen overnight. The next morning, the flask was placed under vacuum; The residual UV-chromophore was sublimed and collected in a distillation adapter. Heating under vacuum was continued overnight. The reaction mixture was then cooled to room temperature; The UV absorbing polyglycerol product was obtained as a yellow, glassy solid. ¹ H NMR (400 ㎒, CDCl ₃ ) δ ppm 11.71 (br.s., 8 H), 8.05 (br.s., 8 H), 7.81 (br.s., 16 H), 7.36 (br.s. ., 16 H), 7.14 (br.s., 8 H), 5.06-5.32 (br.s., 1 H), 3.86-4.57 (m, 16 H), 3.15-3.82 (m, 30 H), 2.92 (br.s., 16 H), 2.68 (br.s., 16 H), 1.45 (br.s., 76 H), 1.24 (br.s., 28 H), 0.88 (t, J = 6.6 ㎐, 3 H).

From Examples 1 to 11, it can be seen that the analytical characteristics of the resulting UV absorbing polyether were consistent with the expected structure. HPLC analysis of the polymers described in the examples provided evidence that the polymerization methods described resulted in low concentrations of residual UV absorbing monomers.

Example 12. Summary of SPF results

Sun protection factor (SPF) was measured for the UV absorbing polymer using the following in vitro sun protection test method. The polymer sample was weighed and placed in an 8 mL glass vial. Mixed C ₁₂ to C ₁₅ alkyl benzoate (cosmetic oil solvent sold under the trade name FINSOLV TN by Innospec, Newark, NJ) to the vial to add the desired weight percent solution of the polymer Was achieved. A magnetic stir bar was added to the vial and then sealed with a Teflon lined screw cap. The polymer/oil solution was stirred in a 100° C. aluminum reaction block until homogeneous. Once cooled, 32 mg of the polymer solution was applied to a poly(methyl methacrylate) (PMMA) plate (test description sold under the trade name HELIOPLATE HD6 by Heliosciences, Marseille, France). The solution was spread evenly over the plate using a latex cot with one finger until the weight of the sample on the plate was reduced to 26 mg. Baseline permeability was measured using the HD6 plate as received from the manufacturer. Absorbance was measured using a calibrated Labsphere UV-1000S UV transmittance analyzer (Labsphere, North Sutton, Hampshire, USA). The SPF index was calculated using absorbance measurements. SPF was calculated using methods known in the art. The equation used to calculate the SPF is described by Equation 1 below:

[Equation 1]

SPF in _vitro = [∫ E(λ) I(λ)dλ] / [∫ E(λ) I(λ) 10 ^-A ₀ ^(λ) (dλ)]

here,

E(λ) = erythema action spectrum

I(λ) = spectral irradiance from UV source

A ₀ (λ) = average single wavelength absorbance of the test product layer before UV exposure

dλ = wavelength step (1 nm)

And, integration was performed over a wavelength range of 290 nm to 400 nm, respectively.

The results of the in vitro SPF test of the polymers are reported in Example 4, Examples 7, and 9 as [% by weight in Finsolve TN, average SPF value] which are also shown in Table 1.

[Table 1]

It can be seen that the described polymer composition was soluble in oils commonly used in topical cosmetic applications. Moreover, solutions of polymers in these oils have been demonstrated to show suitable SPF values when using the in vitro SPF test method.

Composition Examples

The following examples illustrate the low irritation of certain compositions of the invention. The compositions of the present invention (E1 to E3) include a polymer composition comprising a linear ultraviolet radiation absorbing polyether comprising a chemically bound UV-chromophore. The polymer composition was prepared according to the method described in Example 3B and Example 4. The compositions (E1 to E3) of the present invention are shown in Table 2 and prepared as described below.

[Table 2]

Amiel is a sclerotium gum available from Alban Muller International, Haier, Florida, USA. Phenonib XB is phenoxyethanol (and) methylparaben (and) ethylparaben (and) propylparaben, available from Clariant, Mutenz, Switzerland. Pemulen TR-2 is an acrylate/C _10-30 alkyl acrylate crosspolymer available from Noveon/Lubrizol, Wickliffe, Ohio. Cetiol CC is Cognis, Ludwigshafen, Germany, and dicaprylyl carbonate, now available from BASF. Amphisol K is potassium cetyl phosphate (100% anionic) available from DSM, Herlen, The Netherlands. Emulcifos is potassium cetyl phosphate (*60% active anionic) and hydrogenated palm glyceride (40%), available from Symrise, Teterborough, NJ.

Examples E1 to E3 and Comparative Examples C1 to C3 of the present invention were prepared by the following process. The water phase was prepared by adding water to the main vessel and heating to 80° C. while mixing. Amigel, Pemulen TR2, and Penonib XB were added and mixed until dissolved. The oil phase was prepared by filling the container with Cetiol CC and mixing. UV-absorbing polyether was added at 60°C. Amphisol K or Emulcifos was added and the mixture was heated to about 80° C. while mixing. The heated water phase was added to the oil phase with moderate shear. During cooling, normal mixing was continued. To provide homogeneity, Examples E1 to E3 and Comparative Example C3 were homogenized using a Silverson L4RT homogenizer (Silverson Machines, East Long Meadows, Mass.).

The modified TEP values of Examples E1 to E3 and Comparative Examples C1 to C3 of the present invention were determined using the modified TEP as described above, and the results are reported in Table 3.

[Table 3]

The results of the modified TEP test indicate that the examples of the present invention have very low modified TEP values, suggesting surprisingly low stimulation. Conversely, comparative compositions C1 and C3 containing more than about 3% of anionic emulsifier, or less than about 0.5% of anionic emulsifier, have much larger modified TEP values.

Although the present invention has been described together with specific details for carrying out the invention, it is understood that the specific details for carrying out the above-described invention are intended to be illustrative and not limiting the scope of the present invention.

Claims (29)

As a composition,
Continuous awards;
Discrete oil phase homogeneously distributed in the water phase, wherein the oil phase comprises a sunscreen agent comprising a polymer composition, the polymer composition comprising a linear UV radiation absorbing poly comprising a covalently bonded UV-chromophore Ethers); And
Oil-in-water emulsifier component (the oil-in-water emulsifier component comprises an anionic oil-in-water emulsifier in an amount of 0.5% to 3% by weight of the composition),
Here, the linear ultraviolet radiation absorbing polyether

Wherein Y is the covalently bonded UV-chromophore, and x is an integer, the number of repeating units comprising a repeating unit selected from the group consisting of. The composition of claim 1 comprising from 5% to 50% by weight of the linear ultraviolet radiation absorbing polyether. The composition of claim 1, wherein the polymer composition consists of the linear ultraviolet radiation absorbing polyether. The composition of claim 1 comprising 7% to 40% by weight of the linear ultraviolet radiation absorbing polyether. The composition of claim 1 comprising 10% to 25% by weight of the linear ultraviolet radiation absorbing polyether. The composition of claim 1, wherein the composition does not include a non-polymeric UV-absorbing sunscreen agent. 7. The composition of claim 6, wherein the composition does not contain polymeric sunscreens other than the linear ultraviolet radiation absorbing polyether. The composition of claim 1 comprising from 0.6% to 3.0% by weight of the anionic oil-in-water emulsifier. The composition of claim 1 comprising from 0.6% to 2.5% by weight of the anionic oil-in-water emulsifier. The composition of claim 7 wherein the anionic oil-in-water emulsifier component comprises potassium cetyl phosphate. The method of claim 1, wherein the anionic oil-in-water emulsifier is sulfate, ether sulfate, monoglyceryl ether sulfate, sulfonate, sulfosuccinate, ether sulfosuccinate, sulfosuccinate, amidosulfosuccinate, carbohydrate. A group consisting of alkyl, aryl, or alkylaryl, or acyl-modified versions of carboxylate, amidoethercarboxylate, succinate, sarcosinate, amino acid, taurate, sulfoacetate, and phosphate. The composition is selected from. The composition of claim 1, wherein the anionic oil-in-water emulsifier component comprises a phosphate ester. The composition of claim 1, wherein the oil-in-water emulsifier component comprises 1% by weight or less or 0.5% by weight or less of a non-ionic emulsifier having an alcohol-functional group. The composition of claim 1, wherein the oil-in-water emulsifier component comprises 1% by weight or less or 0.5% by weight or less of a cationic emulsifier. The composition of claim 1, wherein the oil-in-water emulsifier component is composed of the anionic emulsifier. The composition of claim 1, wherein the composition has an SPF of 20 or greater. delete The composition of claim 1, wherein the linear ultraviolet radiation absorbing polyether comprises a skeleton having glyceryl repeat units. The composition of claim 1, wherein the linear ultraviolet radiation absorbing polyether has the following structure:

(Where R is a pendant group, Y represents the covalently bonded UV-chromophore, X is a terminal group, m and n are real numbers between 0 and 1, and o and p are each independently 1 or 2 ). 20. The composition of claim 19, wherein m is 1 and n is 0. The composition of claim 20, wherein X and R are independently selected from the group consisting of hydrogen, linear alkyl, alkenyl or alkynyl hydrocarbon chain, and linear siloxane. The method according to claim 1, wherein the UV-chromophore is triazole, camphor (camphor), dibenzoylmethane, 4-aminobenzoic acid and its alkanes esters, anthranilic acid and its alkanes esters, salicylic acid and its alkanes esters, hydroxycinnamic acid And alkane esters thereof, dihydroxy-, dicarboxy-, and hydroxycarboxybenzophenones and alkane esters or acid halide derivatives thereof, dihydroxy-, dicarboxy-, and hydroxycarboxychalcones and alkanes esters or acid halides thereof Derivatives, dihydroxy-, dicarboxy-, and hydroxycarboxycoumarin and alkane ester or acid halide derivatives thereof, benzalmalonates, substituents including benzimidazole, substituents including benzoxazole, 3-(3- (2H-benzo[d][1,2,3]triazole-2-yl)-5-(tert-butyl)-4-hydroxyphenyl), 6-octyl-2-(4-(4,6 -Di([1,1'-biphenyl]-4-yl)-1,3,5-triazine-2-yl)-3-hydroxyphenoxy)propanoate, and trioctyl 2,2' ,2"-(((1,3,5-triazine-2,4,6-triyl) tris(3-hydroxybenzene-4,1-diyl))tris(oxy)) tripropanoate A composition selected from the group consisting of. The composition of claim 1, wherein the UV-chromophore is selected from the group consisting of benzotriazole and triazine. The composition of claim 1, wherein the linear ultraviolet radiation absorbing polyether has a weight average molecular weight in the range of 1000 to 20,000. The composition of claim 1, wherein the polymer composition has a polydispersity index of 1.5 or less. The composition of claim 1, wherein the polymer composition comprises at least 50% by weight of the linear ultraviolet radiation absorbing polyether. The composition of claim 1, wherein the polymer composition comprises at least 95% by weight of the linear ultraviolet radiation absorbing polyether. The composition of claim 1, wherein the composition has an SPF of 10 or greater. The composition of claim 1, wherein the composition has a modified TEP value of 0.3 or less.